Phytochemical and Neuropharmacological Characterization of Newbouldia laevis Reveals GABAergic and Glycinergic Contributions to Its Antiseizure Activity

Newbouldia laevis is widely employed in African traditional medicine for the management of epilepsy and other convulsive disorders. Despite its extensive ethnomedicinal use, the neuropharmacological mechanisms underlying its anticonvulsant activity remain poorly defined. This study investigated the antiseizure potential of N. laevis leaf extract and chromatographic fractions and explored their possible involvement in GABAergic and glycinergic neurotransmission. The ethanol leaf extract of N. laevis was fractionated by column chromatography to obtain three fractions designated N-green, N-pink, and N-yellow. Phytochemical constituents were characterized using gas chromatography–mass spectrometry (GC–MS). Antiseizure activity was evaluated in mice using sodium barbital-induced hypnosis, picrotoxin-induced seizures, and strychnine-induced seizure models. Diazepam served as the reference drug. Seizure latency, seizure duration, sleep parameters, and 24-hour mortality were assessed. The crude extract and N-green fraction significantly potentiated sodium barbital-induced hypnosis, reducing sleep latency and prolonging sleep duration in a dose-dependent manner. In the picrotoxin model, both treatments significantly delayed seizure onset and reduced seizure duration, with the N-green fraction at 600 mg/kg producing effects comparable to diazepam. Furthermore, the crude extract and N-green fraction completely prevented picrotoxin-induced mortality at doses ≥300 mg/kg, whereas diazepam achieved only partial protection. In contrast, neither the extract, fractions, nor diazepam altered seizure parameters or prevented mortality in strychnine-treated mice. GC–MS analysis revealed the presence of several bioactive phytochemicals that may contribute to the observed neuropharmacological effects. Newbouldia laevis exhibits pronounced anticonvulsant and sedative activities, mediated predominantly through GABAA_AA-ergic rather than glycinergic mechanisms. These findings provide pharmacological support for its traditional use in epilepsy management and identify the bioactive fraction as a promising source of lead compounds for the development of novel GABA-targeted antiseizure therapies.